{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:36:40Z","timestamp":1792021000784,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,11,30]],"date-time":"2010-11-30T00:00:00Z","timestamp":1291075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Vasculitis Clinical Research Consortium funded by the NIH\/National Center for Research Resources","award":["U54-RR-019497"],"award-info":[{"award-number":["U54-RR-019497"]}]},{"name":"NIH\/National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["P60-AR-047785"],"award-info":[{"award-number":["P60-AR-047785"]}]},{"name":"NIH\/National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["R01-AR-047799"],"award-info":[{"award-number":["R01-AR-047799"]}]},{"name":"Soci\u00e9t\u00e9 Nationale Fran\u00e7aise de M\u00e9dicine Interne"},{"name":"NIH\/National Heart, Lung, and Blood Institute Mid-Career Development Award in Clinical Investigation","award":["K24-HL-004456"],"award-info":[{"award-number":["K24-HL-004456"]}]},{"name":"NIH\/National Institute of Arthritis and Musculoskeletal and Skin Diseases Mid-Career Development Award in Clinical Investigation","award":["K24-AR-02224"],"award-info":[{"award-number":["K24-AR-02224"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Deficiency of \u03b1<jats:sub>1<\/jats:sub>\u2010antitrypsin (\u03b1<jats:sub>1<\/jats:sub>AT) may be a determinant of susceptibility to Wegener's granulomatosis (WG). Several previous, mainly small, case\u2013control studies have shown that 5\u201327% of patients with WG carried the \u03b1<jats:sub>1<\/jats:sub>AT deficiency Z allele. It is not clear whether the S allele, the other major \u03b1<jats:sub>1<\/jats:sub>AT deficiency variant, is associated with WG. This study investigated the relationship of the \u03b1<jats:sub>1<\/jats:sub>AT deficiency Z and S alleles with the risk of developing WG in a large cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the distribution of the \u03b1<jats:sub>1<\/jats:sub>AT deficiency alleles Z and S in 433 unrelated Caucasian patients with WG and 421 ethnically matched controls. Genotyping was performed using an allele discrimination assay. Results were compared between cases and controls using exact statistical methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the patients with WG, the allele carriage frequencies of Z and S were 7.4% and 11.5%, respectively. The frequencies of the 6 possible genotypes differed in a statistically significant manner between cases and controls (<jats:italic>P<\/jats:italic> = 0.01). The general genetic 2\u2010parameter codominant model provided the best fit to the data. Compared with the normal MM genotype, the odds ratio (OR) for MZ or MS genotypes was 1.47 (95% confidence interval [95% CI] 0.98\u20132.22), and the OR for ZZ, SS, or SZ genotypes was 14.58 (95% CI 2.33\u2013\u221e). ORs of similar direction and magnitude were observed within the restricted cohorts that excluded cases and controls carrying \u22651 Z or \u22651 S allele.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both Z and S alleles display associations with risk of WG in a codominant genetic pattern. These findings strengthen the evidence of a causal link between \u03b1<jats:sub>1<\/jats:sub>AT deficiency and susceptibility to WG.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27742","type":"journal-article","created":{"date-parts":[[2010,9,8]],"date-time":"2010-09-08T16:47:01Z","timestamp":1283964421000},"page":"3760-3767","source":"Crossref","is-referenced-by-count":87,"title":["Alpha<sub>1<\/sub>\u2010antitrypsin deficiency\u2013related alleles Z and S and the risk of Wegener's granulomatosis"],"prefix":"10.1002","volume":"62","author":[{"given":"Alfred D.","family":"Mahr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Edberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. William","family":"St.Clair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Specks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Dellaripa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Spiera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshid N.","family":"Rouhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Brantly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Merkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Wegener's Granulomatosis Genetic Repository Research Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,11,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69114-9"},{"key":"e_1_2_6_3_2","first-page":"S82","article-title":"Epidemiology of Wegener's granulomatosis: lessons from descriptive studies and analyses of genetic and environmental risk determinants","volume":"24","author":"Mahr AD","year":"2006","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1993.186"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1994.tb00842.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0870693"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1995.tb03652.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1996.2070553.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1093\/oxfordjournals.ndt.a027308","article-title":"C\u2010antineutrophil cytoplasmic antibody positivity in vasculitis patients is associated with the Z allele of alpha\u20101\u2010antitrypsin, and P\u2010antineutrophil cytoplasmic antibody positivity with the S allele","volume":"11","author":"Griffith ME","year":"1996","journal-title":"Nephrol Dial Transplant"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1997.1720717.x"},{"key":"e_1_2_6_11_2","first-page":"206","article-title":"Alpha\u20101\u2010antitrypsin phenotyping in ANCA\u2010associated diseases: one of several arguments for protease\/antiprotease imbalance in systemic vasculitis","volume":"14","author":"Esnault VL","year":"1997","journal-title":"Exp Clin Immunogenet"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2000.4962"},{"key":"e_1_2_6_13_2","volume-title":"Epidemiologic research: principles and quantitative methods","author":"Kleinbaum DG","year":"1982"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(02)00209-X"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2003.00143.x"},{"key":"e_1_2_6_16_2","first-page":"406","article-title":"Real time PCR detection of the PI*Z and PI*S mutations associated with alpha\u20101 antitrypsin deficiency","volume":"1","author":"Bartels CL","year":"2009","journal-title":"Am J Transl Res"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.97.2510.137"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1109\/TAC.1974.1100705"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200104)44:4<912::AID-ANR148>3.0.CO;2-5"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.168.7.818"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66781-5"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.360"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500132"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/16.1.39"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(03)00030-3"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030236"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.2003.006494"}],"container-title":["Arthritis &amp; 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